Digital mucous cyst: Altered epidermal mucin as a clue to diagnosis.

BACKGROUND: Digital mucous cyst (DMC) is histopathologically characterized by accumulation of mucin in the dermis. Some cases of DMC also show epidermal mucin, the histopathologic appearance and staining properties of which have not been described in detail. METHODS: A total of 24 cases of DMC were investigated by routine hematoxylin-eosin (H&E) and Alcian blue stains in addition to AE1/AE3 immunohistochemistry. RESULTS: Nine out of the 24 cases of DMC showed epidermal mucin. As the epidermal mucin migrates upward within the epidermis, it transforms from a flocculent granular substance into one or several solid horizontal plugs with a more homogeneous appearance and incorporates cytoplasmic fragments of keratinocytes/corneocytes. The homogeneous mucin plugs stain eosinophilic or amphophilic with an H&E formulation using hematoxylin 7212 and basophilic with Gill 3 or Harris's hematoxylin. The eosinophilic staining is enhanced when the eosin solution contains phloxine. CONCLUSIONS: The variably eosinophilic, amphophilic, or basophilic staining of epidermal mucin can be explained by its composition of basophilic mucin and eosinophilic debris from cytoplasmic fragments. The eosinophilic staining of mucin has not been reported before and can be diagnostically important because it may be mistaken for serum exudate.

Benign Phyllodes Tumor in Children: A Study of 8 Cases and Review of the Literature.

Phyllodes tumor (PT) occurs predominantly in middle-aged women, and although its occurrence in young women, adolescents, and even children is documented, presentation in the pediatric population has been the least well studied because of its rarity. Incompletely defined in children with PT are recurrence rates and optimal surgical management. We retrospectively studied the pathology database of Hartford Hospital from 2010 to 2017 to find all cases of PT in patients 18 years of age or younger. A series of 8 children/adolescents with breast masses diagnosed as benign PT were identified. Patients were 14 to 16 years of age (mean 15.2 y) and tumor size ranged from 2.2 to 7.2 cm (mean 4.4 cm). Both breasts were equally affected. All patients were treated with excision, tantamount to simple enucleation in most cases, and positive or "tumor-abutting" margins were universal. Mean follow-up after surgery was 27.5 months, during which time a single recurrence (at 9 mo) became manifest, which was re-excised and again showed benign PT. There were no pathologic features (including marginal status) that could have predicted the sole recurrence. Despite positive margins, the local recurrence rate for pediatric benign PT appears acceptably low (1 in 8 cases) such that reflex re-excision is probably unnecessary.

Identifying an early treatment window for predicting breast cancer response to neoadjuvant chemotherapy using immunohistopathology and hemoglobin parameters.

BACKGROUND: Breast cancer pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) varies with tumor subtype. The purpose of this study was to identify an early treatment window for predicting pCR based on tumor subtype, pretreatment total hemoglobin (tHb) level, and early changes in tHb following NAC. METHODS: Twenty-two patients (mean age 56 years, range 34-74 years) were assessed using a near-infrared imager coupled with an Ultrasound system prior to treatment, 7 days after the first treatment, at the end of each of the first three cycles, and before their definitive surgery. Pathologic responses were dichotomized by the Miller-Payne system. Tumor vascularity was assessed from tHb; vascularity changes during NAC were assessed from a percentage tHb normalized to the pretreatment level (%tHb). After training the logistic prediction models using the previous study data, we assessed the early treatment window for predicting pathological response according to their tumor subtype (human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), triple-negative (TN)) based on tHb, and %tHb measured at different cycles and evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: In the new study cohort, maximum pretreatment tHb and %tHb changes after cycles 1, 2, and 3 were significantly higher in responder Miller-Payne 4-5 tumors (n = 13) than non-or partial responder Miller-Payne 1-3 tumors (n = 9). However, no significance was found at day 7. The AUC of the predictive power of pretreatment tHb in the cohort was 0.75, which was similar to the performance of the HER2 subtype as a single predictor (AUC of 0.78). A greater predictive power of pretreatment tHb was found within each subtype, with AUCs of 0.88, 0.69, and 0.72, in the HER2, ER, and TN subtypes, respectively. Using pretreatment tHb and cycle 1 %tHb, AUC reached 0.96, 0.91, and 0.90 in HER2, ER, and TN subtypes, respectively, and 0.95 regardless of subtype. Additional cycle 2 %tHb measurements moderately improved prediction for the HER2 subtype but did not improve prediction for the ER and TN subtypes. CONCLUSIONS: By combining tumor subtypes with tHb, we predicted the pCR of breast cancer to NAC before treatment. Prediction accuracy can be significantly improved by incorporating cycle 1 and 2 %tHb for the HER2 subtype and cycle 1 %tHb for the ER and TN subtypes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02092636 . Registered in March 2014.

Management of intraductal papilloma without atypia of the breast diagnosed on core biopsy: Size and sampling matter.

Due to the potential for atypia (atypical ductal or lobular hyperplasia) or carcinoma (in situ or invasive) on excision, aggressive reflex surgical excision protocols following core biopsy diagnosis of papillary lesions of the breast (ie, intraductal papilloma) are commonplace. Concepts in risk stratification, including radiologic-pathologic correlation, are emerging in an effort to curb unnecessary surgeries. To this end, we examined all excised intraductal papillomas diagnosed at our institution from 2010-2015 (N = 336) and found an overall atypia rate of 20%. To investigate further, we stratified all excised papillomas according to total lesion size (range = 1-40 mm) and found that the atypia rate for lesions ≤1.2 cm (16% with atypia) was statistically significantly lower (P = .008) than the atypia rate for lesions >1.2 cm (36% with atypia). To explore to effects of radiologic-pathologic correlation on the ability of the core biopsy to accurately predict nonatypical lesions we assessed thirteen consecutive paired nonatypical core biopsy/follow-up surgical excision specimens for the percent of the total lesion (on imaging) sampled by the core biopsy (measured histologically). None of the thirteen paired specimens showed upgrade on excision (0/13); the percent of total lesion sampled by biopsy in this cohort averaged 59%. We propose that in the absence of discordant clinical/radiological findings, small lesions (≤1.2 cm) with radiologic-pathologic concordance (>50% sampling of total lesion by core biopsy) may safely forego surgery for close clinical and radiographic follow-up.

Micropapillary variant of mucinous breast carcinoma: A distinct subtype.

Invasive micropapillary carcinoma of the breast is a subtype with high malignant potential characterized by lymphovascular invasion (LVI) and a predilection for axillary lymph node (AXLN) metastases. In contrast, pure mucinous breast carcinoma (MBC) is relatively indolent with low metastatic potential. Recent studies have described a histologic variant of breast cancer that displays combined mucinous and micropapillary patterns, ie, micropapillary variant of mucinous carcinoma (MpVMBC). This underrecognized variant is, as yet, incompletely characterized clinicopathologically. Extant reports suggest a more aggressive lesion than pure MBC with greater propensity for both LVI and AXLN metastases. Here we present our institution's experience with MpVMBCs including clinicopathologic and immunohistochemical (IHC) analyses. Greater awareness and recognition of this variant could positively contribute to patient care by (1) avoiding underestimation of malignant potential for individuals whose tumors may have been diagnosed as simply "MBC, not otherwise specified", and (2) recommending a postsurgical adjuvant approach emphasizing the hormone receptor targets, even perhaps in younger women presenting with AXLN positive disease.

Assessment of Functional Differences in Malignant and Benign Breast Lesions and Improvement of Diagnostic Accuracy by Using US-guided Diffuse Optical Tomography in Conjunction with Conventional US.

Purpose To investigate ultrasonography (US)-guided diffuse optical tomography to distinguish the functional differences of hemoglobin concentrations in a wide range of malignant and benign breast lesions and to improve breast cancer diagnosis in conjunction with conventional US. Materials and Methods The study protocol was approved by the institutional review boards and was HIPAA compliant. Written informed consent was obtained from all patients. Patients (288 women; mean age, 50 years; range, 17-94 years) who underwent US-guided biopsy were imaged with a handheld US and optical probe. The US-imaged lesion was used to guide reconstruction of light absorption maps at four wavelengths, and total hemoglobin (tHb), oxygenated hemoglobin (oxyHb), and deoxygenated hemoglobin (deoxyHb) were computed from the absorption maps. A threshold (80 µmol/L) was chosen on the basis of this study population. Two radiologists retrospectively evaluated US images on the basis of the US Breast Imaging Reporting and Data System lexicon, and a lesion was considered malignant when a score of 4C or 5 was given or a lesion had tHb greater than 80 µmol/L. A two-sample t test was used to calculate significance between groups, and Spearman ρ was computed between hemoglobin parameters and tumor pathologic grades. Results Three tumors were Tis, 37 were T1, 19 were T2-T4 carcinomas, and 233 were benign lesions. The mean maximum tHb, oxyHb, and deoxyHb of Tis-T1 and T2-T4 groups were 89.3 µmol/L ± 20.2 (standard deviation), 65.0 µmol/L ± 20.8, and 33.5 µmol/L ± 11.3, respectively, and 84.7 µmol/L ± 32.8, 57.1 µmol/L ± 19.8, and 34.7 µmol/L ± 18.9, respectively. The corresponding values of benign lesions were 54.1 µmol/L ± 23.5, 38.0 µmol/L ± 17.4, and 25.2 µmol/L ± 13.8, respectively. The mean maximum tHb, oxyHb, and deoxyHb were significantly higher in the malignant groups than the benign group (P <.001, <.001, and .041, respectively). For malignant lesions, the mean maximum tHb moderately correlated with tumor histologic grade and nuclear grade (ρ = 0.283 and 0.315, respectively). The mean maximum oxyHb moderately correlated with tumor nuclear grade (ρ = 0.267). When radiologists' US diagnosis and the tHb were used together, the sensitivity, specificity, positive predictive value, and negative predictive value were 96.6%-100%, 77.3%-83.3%, 52.7%-59.4%, and 99.0%-100%, respectively, for the combined malignant group. Conclusion The tHb and oxyHb correlate with breast cancer pathologic grade and can be used as an adjunct to US to improve sensitivity and negative predictive value in breast cancer diagnosis. (©) RSNA, 2016 Online supplemental material is available for this article.

Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria.

INTRODUCTION: The purpose of this study is to develop a prediction model utilizing tumor hemoglobin parameters measured by ultrasound-guided near-infrared optical tomography (US-NIR) in conjunction with standard pathologic tumor characteristics to predict pathologic response before neoadjuvant chemotherapy (NAC) is given. METHODS: Thirty-four patients' data were retrospectively analyzed using a multiple logistic regression model to predict response. These patients were split into 30 groups of training (24 tumors) and testing (12 tumors) for cross validation. Tumor vascularity was assessed using US-NIR measurements of total hemoglobin (tHb), oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) concentrations acquired before treatment. Tumor pathologic variables of tumor type, Nottingham score, mitotic index, the estrogen and progesterone receptors and human epidermal growth factor receptor 2 acquired before NAC in biopsy specimens were also used in the prediction model. The patients' pathologic response was graded based on the Miller-Payne system. The overall performance of the prediction models was evaluated using receiver operating characteristic (ROC) curves. The quantitative measures were sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC). RESULTS: Utilizing tumor pathologic variables alone, average sensitivity of 56.8%, average specificity of 88.9%, average PPV of 84.8%, average NPV of 70.9% and average AUC of 84.0% were obtained from the testing data. Among the hemoglobin predictors with and without tumor pathological variables, the best predictor was tHb combined with tumor pathological variables, followed by oxyHb with pathological variables. When tHb was included with tumor pathological variables as an additional predictor, the corresponding measures improved to 79%, 94%, 90%, 86% and 92.4%, respectively. When oxyHb was included with tumor variables as an additional predictor, these measures improved to 77%, 85%, 83%, 83% and 90.6%, respectively. The addition of tHb or oxyHb significantly improved the prediction sensitivity, NPV and AUC compared with using tumor pathological variables alone. CONCLUSIONS: These initial findings indicate that combining widely used tumor pathologic variables with hemoglobin parameters determined by US-NIR may provide a powerful tool for predicting patient pathologic response to NAC before the start of treatment. TRIAL REGISTRATION: ClincalTrials.gov ID: NCT00908609 (registered 22 May 2009).

Breast cancer: assessing response to neoadjuvant chemotherapy by using US-guided near-infrared tomography.

PURPOSE: To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response. MATERIALS AND METHODS: The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons. RESULTS: There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively). DISCUSSION: These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Early-stage invasive breast cancers: potential role of optical tomography with US localization in assisting diagnosis.

PURPOSE: To investigate the potential role of optical tomography in the near-infrared (NIR) spectrum with ultrasonographic (US) localization as a means of differentiating early-stage cancers from benign lesions of the breast. MATERIALS AND METHODS: The protocol was approved by the institutional review boards and was HIPAA compliant; all participants signed an informed consent. One hundred seventy-eight consecutive women (mean age, 52 years; range, 21-89 years) who underwent US-guided biopsy were imaged with a hand-held probe consisting of a coregistered US transducer and an NIR imager. The lesion location provided by coregistered US was used to guide optical imaging. Light absorption was measured at two optical wavelengths. From this measurement, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration (tHb) and was correlated with core biopsy results. For patients diagnosed with carcinomas and followed up with subsequent excision, the tHb was correlated with pathologic parameters. RESULTS: There were two in situ carcinomas (Tis), 35 T1 carcinomas, 24 T2-T4 carcinomas, and 114 benign lesions. The mean maximum and mean average tHb of the Tis-T1 group were 102.0 micromol/L +/- 28.5 (standard deviation) and 71.9 micromol/L +/- 18.8, and those of the T2-T4 group were 100.3 micromol/L +/- 26.4 and 67.0 micromol/L +/- 18.3, respectively. The mean maximum and mean average tHb of the benign group were 55.1 micromol/L +/- 22.7 and 39.1 micromol/L +/- 14.9, respectively. Both mean maximum and mean average tHb levels were significantly higher in the malignant groups than they were in the benign group (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value for Tis-T1 cancers were 92%, 93%, 81%, and 97%. The corresponding values for T2-T4 tumors were 75%, 93%, 69%, and 95%. CONCLUSION: The angiogenesis (tHb) contrast imaged by using the NIR technique with US holds promise as an adjunct to mammography and US for distinguishing early-stage invasive breast cancers from benign lesions.

Prevalence and significance of perineural invasion in invasive breast carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic feature in breast cancer. Perineural invasion (PNI), a sign of aggressive behavior potential in other tumor systems, is less frequently observed in mammary carcinoma and hence has been less well studied. The present work was conducted to determine the frequency of PNI in mammarycarcinoma and to describe the relationships between PNI, tumor characteristics (including LVI) and clinical outcome. DESIGN: The Hartford Hospital pathology database was reviewed for cases of invasive mammary carcinoma diagnosed from 2000-2002. The search was then narrowed to include only those cases reporting PNI, LVI, or both. These targeted reports were then reviewed to abstract clinicopathologic data with regard to patient age, tumor stage and nuclear/ histologic grade. Histologic review was performed on all PNI(+)cases. Comparisons between tumor characteristics associated with PNI and LVI were generated. Nodalstatus andpatientoutcomewereobtainedfrom cancer registry records. RESULTS: From a total of 1136 cases of invasive mammary carcinoma diagnosed from 2000-2002, 13 (1.14%) and 146 (12.9%) showed PNI and LVI, respectively. Of the 13 patients with PNI, 5/13 (38.5%) also had LVI. Both PNI and LVI were associated with higher T-stage and intermediate to high NG/HG. CONCLUSIONS: PNI is a relatively rare histologic feature in invasive breast carcinoma occurring 10 times less frequently than LVI. Tumor characteristics associated with PNI include higher T-stage, higher tumor grade and LVI. Despite this, patients with PNI can expect a meaningful survival at five years with appropriately aggressive adjuvant therapy (only one of 13 patients in this study was known DOD after mean follow-up of 5.9 yr). When observed in tissue sections PNI should be reported (for completeness) but its role as an independent poor prognostic feature remains questionable.